Investigation of the Mechanism of Cold Hyperalgesia in KOA Mice Relieved by Shangke Lengtongtie Based on HMGB1/CX-CL12/CXCR4 Signaling Axis
10.14148/j.issn.1672-0482.2025.0195
- VernacularTitle:基于HMGB1/CXCL12/CXCR4信号轴探讨伤科冷痛贴缓解KOA小鼠冷痛敏的机制研究
- Author:
Yibao WEI
1
;
Li ZHANG
;
Taiyang LIAO
;
Lishi JIE
;
Zhenyuan MA
;
Peng WU
;
Zhengquan HUANG
;
Li ZHANG
;
Liang DING
;
Wei MEI
;
Runlin XING
;
Songjiang YIN
;
Xiaochen LI
;
Nongshan ZHANG
;
Jun MAO
;
Pei-min WANG
Author Information
1. 南京中医药大学附属医院,江苏 南京 210029;南京中医药学大学代谢病中医研究重点实验室,江苏 南京 210023
- Publication Type:Journal Article
- Keywords:
knee osteoarthritis;
Shangke Lengtongtie;
synovial inflammation;
cold hyperalgesia;
HMGB1/CXCL12/CXCR4;
in vi-vo imaging;
training immunity
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(2):195-202
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.
